Abstract
Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.
Highlights
Gastric cancer remains a critical cancer; the incidence rate of gastric cancer ranks the fifth globally [1]
We found that PLEK2 was remarkably upregulated in the RNA-seq dataset of 444 gastric cancer samples (Figure 1(a))
The DEP domain is in the center, and the two pleckstrin homology (PH) domains are in the amino- and carboxyl-terminals, which are important for PLEK2 colocalization with the actin cytoskeleton at the immune synapse and integrin clusters and involve a broad range of cellular functions [10,11,12,13]
Summary
Gastric cancer remains a critical cancer; the incidence rate of gastric cancer ranks the fifth globally [1]. The diagnosis and management of gastric cancer have improved, the overall survival rate has not increased remarkably [2, 3]. The potential pathways and molecular mechanisms underlying gastric cancer development are still not fully elucidated [4, 5]. The human pleckstrin-2 (PLEK2) gene is located on chromosome 14q24.1 [6]. PLEK2 encompasses two conserved pleckstrin homology (PH) domains and an intervening disheveled-Egl-10-pleckstrin (DEP) domain. The expression of PLEK2 was found in various adherent cell lines [7]. PLEK2 promotes the shape changes associated with actin rearrangement. The expression of PLEK2 and its role in gastric cancer progression and pathogenesis are still elusive
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